Abstract
Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that are implicated in the regulation of information flow in the CA1 circuit, inhibiting cortical inputs to distal pyramidal cell dendrites, whilst disinhibiting CA3 inputs to pyramidal cells. OLM cells express metabotropic cholinergic (mAChR) and glutamatergic (mGluR) receptors, so modulation of these cells via these receptors may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify OLM cells, we found that both mAChR and mGluR activation caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both mAChR- and mGluR-induced plateau potentials were eliminated by blocking transient receptor potential (TRP) channels, and were dependent on intracellular calcium concentration and calcium entry. Pharmacological tests indicated that Group I mGluRs are responsible for the glutamatergic induction of plateaus. There was also a pronounced synergy between the cholinergic and glutamatergic modulation, plateau potentials being generated by agonists applied together at concentrations too low to elicit any change when applied individually. This synergy could enable OLM cells to function as coincidence detectors of different neuromodulatory systems, leading to their enhanced and prolonged activation and a functional change in information flow within the hippocampus.
Highlights
Hippocampal CA1 pyramidal cells receive two different streams of input: one from the entorhinal cortex (EC) conveying a representation of the present external world, and another from the hippocampal CA3 region conveying mnemonic information from past experiences (Vago et al, 2007).Oriens-lacunosum moleculare (OLM) cells are inhibitory interneurons located in the CA1 region, and their activation has been implicated in regulating information flow in the hippocampus, facilitating CA3 input whilst weakening the EC input (Leão et al, 2012).The CA1 network shifts rhythmically between responding to one or the other stream of input (Colgin et al, 2009)
When recording from our genetically labeled OLM cells (n = 14) in Chrna2 transgenic mice, we always observed spontaneous firing of action potentials (3 ± 0.74 Hz) in both cell-attached voltage clamp (Figures 1Ai–ii) and whole-cell current clamp recordings (Figures 1Bi–ii) during control conditions. Such spontaneous firing has previously been reported in OLM cells in acute slice preparations (Leão et al, 2012) and we began by testing whether this firing was modulated by metabotropic cholinergic (mAChR) or metabotropic glutamatergic (mGluR) activation
We sought to determine whether the increase in spontaneous firing seen in OLM cells following activation of these receptors was due to their suppression of Kv7 channels
Summary
Hippocampal CA1 pyramidal cells receive two different streams of input: one from the entorhinal cortex (EC) conveying a representation of the present external world, and another from the hippocampal CA3 region conveying mnemonic information from past experiences (Vago et al, 2007).Oriens-lacunosum moleculare (OLM) cells are inhibitory interneurons located in the CA1 region, and their activation has been implicated in regulating information flow in the hippocampus, facilitating CA3 input whilst weakening the EC input (Leão et al, 2012).The CA1 network shifts rhythmically between responding to one or the other stream of input (Colgin et al, 2009). OLM cells somata are located in the oriens-alveus layer of the CA1, with dendrites that branch within the oriens layer where they receive glutamatergic input from local CA1 pyramidal cells (Blasco-Ibáñez and Freund, 1995) and cholinergic input from the medial septum (Leão et al, 2012). Their axons project to the lacunosum-moleculare layer, where they mediate pre- and post-synaptic inhibition of input to the distal apical dendritic tufts of hippocampal pyramidal cells and disinhibition to pyramidal cell proximal dendrites (McBain et al, 1994; Sik et al, 1995; Leão et al, 2012)
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